Comparing [225Ac]Ac-SibuDAB With [225Ac]Ac-PSMA-617 for Targeted Alpha Therapy of Prostate Cancer

By Emily Menendez - November 29, 2022

A recent study published in Cancers compared the effectiveness of SibuDAB, an albumin-binding prostate-specific membrane antigen (PSMA) ligand, in combination with actinium-225 with [225Ac]Ac-PSMA-617 for the treatment of prostate cancer.

In vitro testing found [225Ac]Ac-SibuDAB and [225Ac]Ac-PSMA-617 to have similar rates of tumor cell uptake and PSMA-binding abilities compared with their 177Lu-labeled counterparts. When compared with [177Lu]Lu-SibuDAB, [225Ac]Ac-SibuDAB was found to have a 2.8-fold increase for in vitro binding to mouse blood and a 1.4-fold increase for in vitro binding to human blood. During in vivo testing, [225Ac]Ac-SibuDAB also had a longer retention in the blood than what was previously seen for [177Lu]Lu-SibuDAB.

[225Ac]Ac-SibuDAB and [225Ac]Ac-PSMA-617 were both well-tolerated in test mice at 30 kBq per mouse, and no major variations were seen between blood cell counts for the 2 treatments. [225Ac]Ac-SibuDAB was found to be more effective than [225Ac]Ac-PSMA-617 for the treatment of PSMA-positive tumor xenografts, as only 5 kBq per test mouse was enough to eradicate the tumors. Tumor regrowth was seen in mice treated with 5 kBq of [225Ac]Ac-PSMA-617, and only 1 out of 6 mice survived through the end of the study.

The enhanced therapeutic effects and positive safety data of [225Ac]Ac-SibuDAB compared with [225Ac]Ac-PSMA-617 qualifies the novel radioligand as a new candidate for the targeted alpha therapy treatment of prostate cancer.